This invention relates to the treatment of obesity with an alpha-2-adrenergic agonist and a growth hormone releasing peptide to induce growth hormone secretion in a patient with this condition.
It is generally known that obese patients have impaired growth hormone (GH) release, both in basal conditions and in response to a number of stimuli, including growth hormone releasing hormone (GHRH, also identified as GRF) (1,2,3,4). This has been postulated to be the result of a hypothalamic disorder (3), leading to a chronic state of somatostatin hypersecretion (5).
It is also known that administering to a normal patient an agent that interferes with the hypothalamic release of somatostatin will enhance growth hormone release. This effect has been shown for clonidine, an alpha-2-adrenergic agonist, and pyridostigmine, a cholinergic agonist, although the mechanism of action is different for each drug (6). Likewise, galanin has been shown to potentiate GHRH induced GH secretion in normal subjects (7) via the cholinergic pathways (8). It has also been recently shown that treatment of obese patients with the cholinergic agonist pyridostigmine will moderately restore the growth hormone responsiveness to GHRH administration, although to a substantially lesser degree than in normal subjects (5,11). While it has been shown that treatment of normal children and adults with clonidine and GHRH has resulted in significantly enhanced growth hormone levels (9,10), it was not known whether such treatment could be extended to obese patients given the lack of response by such patients to most other known treatments.